title: IFN-γ (+874) and not TNF-α (-308) is associated with HBV-HCC risk in India.
abstract: Tumor necrosis factor (TNF)-α and interferon (IFN)-γ, the pro-inflammatory Th1 cytokines are the indispensable coordinators of the inflammatory responses involved in hepatitis B virus (HBV) pathogenesis. This study attempted to evaluate any possible association among TNF-α (-308G>A) and IFN-γ (+874T/A) genotypes, the spontaneous blood and mRNA levels and expression of their major signal transducers, namely STAT1 and NF-кB with hepatitis B virus-induced hepatocellular carcinoma (HCC) susceptibility in India. For this, 398 subjects (146 controls, 68 inactive-HBV-carriers, 64 chronic-active HBV patients, 61 HBV-cirrhotics, and 59 HBV-HCC subjects) were enrolled. Polymerase chain reaction-restriction fragment length polymorphism, allele-specific PCR, enzyme-linked immunosorbent assay, reverse transcriptase-PCR, and Western blot analysis were done for assessing polymorphism, blood levels, mRNA expression, and protein expression of signal transducers, respectively, of TNF-α and IFN-γ. The study revealed no significant association of TNF-α (-308) GA genotype, while a significant negative association of IFN-γ (+874) TA and AA genotypes, in HBV-HCC risk. Moreover, blood levels of TNF-α were significantly elevated as disease progresses to HCC, while IFN-γ levels were raised in HCC patients only. Besides, IFN-γ mRNA levels were significantly elevated in cirrhotics, with no change observed in TNF-α transcript levels. Moreover, NF-кB expression also consistently increased during HCC progression. These observations suggest a vital negative association of IFN-γ (+874) with HBV-HCC risk, with no significant association evident in TNF-α (-308). However, the TNF-α and IFN-γ levels markedly increased in HCC development.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India.
authors.forename: Roli
authors.initials: R
authors.lastname: Saxena
authors.forename: Yogesh Kumar
authors.initials: YK
authors.lastname: Chawla
authors.forename: Indu
authors.initials: I
authors.lastname: Verma
authors.forename: Jyotdeep
authors.initials: J
authors.lastname: Kaur
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006515:Hepatitis B virus / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D007194:India; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma